Distribution, targeting, and internalization of the sst(4) somatostatin receptor in rat brain

Somatostatin mediates its diverse physiological effects through a family of five G-protein-coupled receptors (sst(1)-sst(5)); however, knowledge about the distribution of individual somatostatin receptor proteins in mammalian brain is incomplete. In the present study, we have examined the regional a nd subcellular distribution of the somatostatin receptor sst(4) in the rat CNS by raising anti-peptide antisera to the C-terminal tail of sst4. The sp ecificity of affinity-purified antibodies was demonstrated using immunofluo rescent staining of HEK 293 cells stably transfected with an epitope-tagged sst(4) receptor. In Western blotting, the antiserum reacted specifically w ith a broad band in rat brain, which migrated at similar to 70 kDa before a nd similar to 50 kDa after enzymatic deglycosylation. sst(4)-like immunorea ctivity was most prominent in many forebrain regions, including the cerebra l cortex, hippocampus, striatum, amygdala, and hypothalamus. Analysis at th e electron microscopic level revealed that sst(4)-expressing neurons target this receptor preferentially to their somatodendritic domain. Like the sst (2A) receptor, sst4 immunoreactive dendrites were often closely apposed by somatostatin-14-containing fibers and terminals. However, unlike the sst(2A ) receptor, sst(4) was not internalized in response to intracerebroventricu lar administration of somatostatin-14. After percussion trauma of the corte x, neuronal sst(4) receptors progressively declined at the sites of damage. This decline coincided with an induction of sst(4) expression in cells wit h a glial-like morphology. Together, this study provides the first descript ion of the distribution of immunoreactive sst4 receptor proteins in rat bra in. We show that sst4 is strictly somatodendritic and most likely functions in a postsynaptic manner. In addition, the sst(4) receptor may have a prev iously unappreciated function during the neuronal degeneration-regeneration process.